Project Summary/Abstract Primary visual cortex (V1) is the best studied part of the brain in multiple different mammalian species. Macaque V1 has been particularly intensively studied because of the close homologies between the visual systems of macaques and humans. We understand a great deal about the visual response properties of V1 neurons but, aside from some rough ideas about parallel pathways, we have limited understanding of how the cortical circuit transforms the visual information it receives. The rough outline of the cortical network is known, such as the axonal pathways that distribute information between the layers, but little is known of the network structure of connections between individual neurons. In particular, almost nothing is known about how visual response properties of neurons relate to their interconnections, even for pairs of neurons let alone over the entire network. Over the past decade, we have developed a new approach to studying cortical circuits?functional connectomics?that promises to address this question. Microscale connectomics has been developed by multiple groups with the goal of densely or completely mapping individual synaptic connections in the neural circuits with serial-section electron microscopy. Functional connectomics seeks to relate network structure with the physiological properties of individual neurons within a circuit. So far, virtually all research in microscale connectomics has been performed on mice or non-mammalian species. With recent advances in the scale of volumetric EM reconstructions and machine segmentation, it is time to perform cortical connectomics in species whose physiology is far better understood. In the macaque, we will use two-photon calcium imaging to record the visual responses of tens of thousands of neurons in a single circuit. This same circuit will then be reconstructed with EM connectomics, yielding a data set with rich information about visual response properties, neuronal type (as classified through morphology), and connectivity. This data set will be used to explore competing models of information in the macaque visual system. The close homology between macaque and human V1 offers a unique opportunity to compare their detailed network structure, while the structure/function relationships learned for the macaque will build a bridge for understanding the human network in a functional context.